Effects of Paeoniflora on Blood Pressure and Vascular Endothelial Function in Salt-sensitive Hypertensive Rats by Regulating PI3K/AKT/mTOR Signaling Pathway
Objective:To observe the effect of Paeoniflorin on blood pressure and vascular endothelial function in salt-sensitive hypertensive(SSH)rats and its mechanism.Methods:Fifty Dahl salt-sensitive rats were randomly divided into normal control group,high salt group(SSH group),Paeoniformin group(PF group),Phosphatidylinositol-3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)signaling pathway activator group 740Y-P,paeoniformin +740Y-P group(PF+740Y-P group),with 10 rats in each group.The rats in each group were treated with drug intervention for 4 weeks.Rat tail artery systolic and diastolic blood pressure were measured by animal by animal non-invasive sphygmomanometer.The serum levels of endothelin-1(ET-1),nitric oxide(NO)and thromboxane B2(TXB2)were detected by enzyme-linked immunosorbent assay(ELISA).Hematoxylin-eosin(HE)staining was used to observe the pathological changes of aorta in rats.The protein expression of endothelial nitric oxide synthetase(eNOS)in rat aorta was detected by immunohistochemical staining.The expression of PI3K/AKT/mTOR signaling pathway in rat aorta was detected by Western Blot.Results:Compared with the Control group,the aortic endothelium in the SSH group and the 740Y-P group was incomplete,part of the vascular endothelium was detached,the intima was obviously proliferated,and there were large amounts of deposits in the outer membrane.The pathological damage of aorta vessels in the PF group was significantly less than that in SSH group.The pathological damage of aorta in the PF+740Y-P group significantly decreased than that in the 740Y-P group,but significantly aggravated than that in the PF group.Compared with the Control group,systolic blood pressure,diastolic blood pressure,serum ET-1 and TXB2 levels increased in SSH group,while serum NO level decreased(P<0.05).The expression level of eNOS in aortic tissues decreased,while the phosphorylation(p)-PI3K/PI3K,p-AKT/AKT and p-mTOR/mTOR increased(P<0.05).Compared with the PF group,systolic blood pressure,diastolic blood pressure,serum ET-1 and TXB2 levels in the PF+740Y-P group increased,while the serum NO level decreased(P<0.05).The expression level of eNOS in aortic tissues decreased,while the p-PI3K/PI3K,P-AKT/AKT and p-mTOR/mTOR increased(P<0.05).Compared with the 740Y-P group,systolic blood pressure,diastolic blood pressure,serum ET-1 and TXB2 levels in the PF+740Y-P group decreased,while the serum NO level increased(P<0.05).The expression level of eNOS in aortic tissues increased,and the p-PI3K/PI3K,p-AKT/AKT and p-mTOR/mTOR decreased(P<0.05).Conclusion:Paeoniflora could effectively reduce blood pressure and improve vascular endothelial function in SSH rats,and its mechanism might be related to inhibiting the activation of PI3K/AKT/mTOR signaling pathway.
salt-sensitive hypertensionPaeoniflorinblood pressurevascular endothelial functionphosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin signaling pathwayexperimental study
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万方数据
维普
